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Despite all the beneficial effects of IGF-I described up to now and the following ones reporting its role in aging-related pathologies as musculoskeletal, neurodegenerative, cardiovascular diseases, IGF-I has been paradoxically negatively related to lifespan[266, 267], probably due, at least in part, to its downstream molecule Akt and its interactions with FOXO, mTOR and SIRT-1, among others[268, 269]